Contrasting Case-Control and Normative Reference Approaches to Capture Clinically Relevant Structural Brain...

Area of Science:

• Neuroscience
• Psychiatry
• Radiology

Background:

• Precision psychiatry requires understanding individual variations within biological norms, moving beyond traditional case-control studies.
• Subcortical brain volume deviations may offer a more nuanced view of pathology than raw volumes in first-episode psychosis (FEP).

Purpose of the Study:

• To assess if baseline deviations from normative subcortical volumes predict antipsychotic treatment response in FEP patients.
• To compare the predictive power of volume deviations versus raw volumes for treatment response in antipsychotic-naive FEP patients.

Main Methods:

• A prospective longitudinal study involving 98 antipsychotic-naive FEP patients and 92 controls.
• Patients received 16 weeks of risperidone or aripiprazole treatment.
• Baseline subcortical volumes and deviations from normative ranges were quantified.

Main Results:

• Patients with FEP showed lower raw volumes in several subcortical regions including the thalamus, hippocampus, amygdala, ventral diencephalon, and brainstem.
• 36% of FEP patients exhibited extreme volume deviations.
• Predictive associations with treatment response differed significantly between raw volume and deviation measures for the caudate and putamen.

Conclusions:

• Normative modeling effectively captures interindividual heterogeneity in brain volumes for FEP patients.
• Characterizing structural brain pathology via normative deviations shows promise for advancing precision medicine in psychiatry.
• This approach offers a clinically relevant way to map structural pathology, overcoming limitations of group-level studies.